Actions of Insulin and Insulin-Like Growth Factor-1 on Sterol-Metabolizing Gene Expression in Ovarian Cells

This chapter discusses the effects of insulin and insulin-like growth factor-1 (IGF-1) on sterol-metabolizing gene expression in ovaries. The mammalian female reproductive cycle is an intricately regulated process. In normal physiology, insulin-like peptides and gonadotropic hormones such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) initiate signaling cascades that are critical for follicular growth, ovulation, luteinization, steroidogenesis, fertilization, and successful implantation. The pituitary gonadotropins, FSH and LH, play primary roles in directing steroid-hormone biosynthesis and cognate gene expression. In addition, insulin, insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), members of the transforming growth factor-beta (TGF-b) family (for example, inhibin, activin, and follistatin), bone morphogenetic protein (BMG), and growth differentiation factor (GDF) contribute to cytodifferentiative control. This chapter highlights the physiological importance of insulin and IGF-1 in steroidogenic gene regulation where relevant transgenic (murine) models are illustrated. The pleiotropic effects of IGF-1 and insulin on cellular metabolism, mitogenesis, apoptosis, and survival and cytodifferentiation are mediated by a complex network of intracellular signaling pathways. Signaling is initiated by ligand-specific activation of cell surface receptors with intrinsic tyrosine kinase activity. Proximate kinase substrates include the receptor itself and several insulin-receptor substrates (IRS) such as IRS-1, IRS-2, IRS-3, and IRS-4.